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Key Points
➤ At least 1% of the population uses chronic glucocorticoids (GC) as
anti-inflammatory or immunosuppressive agents
➤ Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an
inevitable effect of chronic exogenous glucocorticoid therapy, and
recovery of adrenal function varies greatly amongst individuals.
➤ Even low dose glucocorticoid use (prednisone 2.5–7.5 mg/day)
increases risks of cardiovascular disease, severe infections,
hypertension, diabetes, osteoporosis and fractures, and increases
overall mortality with concurrent type 2 diabetes mellitus.
➤ Glucocorticoid exposure via oral administration that poses risk
for adrenal insufficiency is expected to at least exceed both of the
following thresholds:
• Duration of glucocorticoid therapy to pose risk for adrenal insufficiency: 3–4 weeks
or greater.
• Dose of glucocorticoid therapy to pose risk for adrenal insufficiency: any dose
greater than daily hydrocortisone equivalent of 15–25 mg (4–6 mg prednisone or
prednisolone, 3–5 mg methylprednisone, 0.25–0.5 mg dexamethasone).
• Physiologic daily dose equivalent: Daily glucocorticoid dose equivalent to average daily
cortisol production (15–25 mg hydrocortisone, 4–6 mg prednisone or prednisolone, 3–5
mg methylprednisone, 0.25–0.5 mg dexamethasone). Endogenous production of cortisol
is estimated to be 9–10 mg/day. The above mentioned doses are based on an estimate of
bioavailability.
• Supraphysiologic glucocorticoid therapy: Any dose greater than physiologic daily dose
equivalent (see above).
• Short-term glucocorticoid therapy: Any glucocorticoid therapy of less than 3–4 weeks
duration.
• Long-term glucocorticoid therapy: Glucocorticoid therapy greater than 3–4 weeks
duration with glucocorticoid doses greater than physiologic daily dose equivalent of
hydrocortisone (15–25 mg hydrocortisone, 4–6 mg prednisone or prednisolone, 3–5 mg
methylprednisone, 0.25–0.5 mg dexamethasone).
• Glucocorticoid taper: Taper of glucocorticoid therapy dose, initially guided by the
management of the underlying disease (= therapeutic taper), and later by the management of
glucocorticoid withdrawal and adrenal insufficiency (= endocrine taper).
• Glucocorticoid withdrawal syndrome: Symptoms experienced when lowering
glucocorticoid dose within the supraphysiologic glucocorticoid dose range, that are not
due to the underlying disease for which the glucocorticoids were initially prescribed for
and per definition not due to untreated adrenal insufficiency, as the total glucocorticoid
daily dose is still supraphysiologic.
Definitions
